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Category: genetics

Parkinson Disease SNCA Risk Variants Are Associated With Higher Asymmetric Putamen Dopaminergic Dysfunction

This study assessed the endophenotypic potential of striatal dopamine transporter uptake in carriers of Parkinson disease–associated SNCA genetic risk variants.

ObjectivesThe aim of this study was to investigate the endophenotypic potential of striatal dopamine transporter (DAT) uptake in carriers of Parkinson disease (PD)–associated SNCA genetic risk variants. MethodsWe analyzed 381 patients with de novo PD from the Parkinson’s Progression Markers Initiative (PPMI). The genotype of previously identified PD-related SNCA risk variants was extracted and used to compute an individual PD-specific SNCA genetic risk score (GRS). Striatal DAT uptake was quantified using 123 I‐FP‐CIT SPECT and assessed at baseline and 24-month follow-up. Mixed models were applied to explore the relationship between striatal 123 I‐FP‐CIT SPECT specific binding ratios (SBRs) and PD SNCA risk variants.

How Dad’s Fitness May Be Packaged and Passed Down in Sperm RNA

We tend to emphasize the maternal role in development: an egg cell is enormous compared to a sperm cell, and a mother gestates the embryo. But a growing body of research suggests that sperm cells carry more than just genetic information.

Research into how a father’s choices — such as diet, exercise, stress, nicotine use — may transfer traits to his children has become impossible to ignore.

Electromagnetic wireless remote control of mammalian transgene expression

An intriguing paper by Lin et al. where cells were engineered to express a signaling pathway that transcribes a gene of interest upon generation of reactive oxygen species (ROS) by CBCFO nanoparticles in response to applied electromagnetic fields. When implanted in a mouse model of diabetes, nanoparticle-treated genetically engineered cells produced insulin and decreased blood glucose levels in the mice after electromagnetic field application.

Wireless magnetic control of gene expression in mammalian cells has been developed based on intracellular nanointerface and ROS-mediated signalling. The approach allows remotely tunable insulin release and regulates blood glucose in diabetic mice.

New antivirals are being tested for herpesviruses, and scientists now know how they work

Harvard Medical School researchers have uncovered crucial insights into how an emerging class of antiviral drugs works.

The discovery sheds light on an important tool for fighting drug-resistant strains of herpes simplex virus, or HSV, and points to new pathways for treating herpesviruses and other kinds of DNA viruses (those that have DNA as their genetic material and can replicate inside host cells).

The study is published in Cell.

A protein that makes hydrogen sulfide shows potential as a therapeutic target for Alzheimer’s disease

Scientists at Johns Hopkins Medicine say results of a new study are advancing efforts to exploit a new target for Alzheimer’s disease: a protein that manufactures an important gas in the brain.

Experiments conducted in genetically engineered mice reinforce that the protein, Cystathionine γ-lyase, or CSE—ordinarily known for producing hydrogen sulfide gas responsible for the foul smell of rotten eggs—is critical for memory formation, says Bindu Paul, M.S., Ph.D., associate professor of pharmacology, psychiatry and neuroscience at the Johns Hopkins University School of Medicine, who led the study.

The new research, published in Proceedings of the National Academy of Sciences, was designed to better understand the basic biology of the protein, and its value as a novel target for drugs that boost the expression of CSE in people to help keep brain cells healthy and slow neurodegenerative disease.

Pathogenic Variants in Hypertrophic and Dilated Cardiomyopathies

Polygenic scores for hypertrophic and dilated cardiomyopathies independently and oppositely modified disease risk and penetrance of pathogenic variants, supporting bidirectional genetic influences on Cardiomyopathy.

Question How is risk of hypertrophic and dilated cardiomyopathy modified by polygenic background?

Findings In this cross-sectional study including 49 434 individuals in the Penn Medicine BioBank, polygenic scores for hypertrophic and dilated cardiomyopathies were associated with clinical and echocardiographic measures relevant to both diseases and inversely modified the penetrance of pathogenic variants.

Meaning The findings indicate that polygenic background exists on an overlapping, opposing spectrum and may contribute to hypertrophic and dilated cardiomyopathy susceptibility.

Researchers at Oregon Health & Science University have developed a proof-of-concept technique to turn human skin cells into egg cells

Marking a first in reproductive science. The process involved transferring skin cell nuclei into donated eggs and stimulating them to behave like natural oocytes, some of which developed into early embryos in the lab. While none progressed beyond a few days and major safety hurdles remain, the study suggests a future path that could one day help women with infertility and expand options in reproductive medicine.

#science #medicine #genetics #fertility #research

Integrating Vascular Aging and Genetic Risk: The Combined Impact of Estimated Pulse Wave Velocity and Genetic Predisposition on Coronary Artery Disease

Vascular aging and genetic risk jointly shape coronary artery disease susceptibility across races and sexes.

BackgroundEstimated pulse wave velocity (ePWV), a noninvasive marker of arterial stiffness, reflects vascular aging and has been associated with increased coronary artery disease (CAD) risk. However, the interplay between ePWV and genetic factors, including polygenic risk score (PRS) and apolipoprotein E genotypes, in determining CAD susceptibility remains unclear.

Monogenic Mimics of Neuroinflammatory Phenotypes in Children and Young AdultsAn Evolving Landscape

This review examines some of the monogenic disorders that can masquerade as neuroinflammatory phenotypes.

A recent explosion in genomic testing has led to the identification of several genetic disorders that mimic CNS-specific autoimmune disorders. Such monogenic disorders, although rare, represent a diagnostic challenge because of their diverse phenotypes and overlapping features. Early recognition of these disorders is crucial not only to prevent overtreatment with immunotherapy but also to ensure that targeted treatments are available for many of these disorders. This review explores some of the monogenic disorders that can masquerade as neuroinflammatory phenotypes. These clinical vignettes are stratified according to neuroanatomical localization along the neuroaxis: supratentorial white matter, gray matter, brainstem, and spinal cord involvement.

Controlled colonization of the human gut with a genetically engineered microbial therapeutic

Great paper highlighting key challenges for genetically engineered bacterial therapies in the human gut. It is respectable that this paper was published in Science despite some “negative” results. Although the genetically engineered bacteria were all supposed to die after removal of porphyrin from the diet, they sometimes rebounded. Even with an improved porphyrin pathway which was supposed to resist mutational rebound, the bacteria still persisted in a mouse model, apparently by mysterious non-mutational means. Maybe the microbiomes of the mice somehow supplied porphyrin to the bacteria without the knowledge of the researchers. Furthermore, therapeutic application of the genetically engineered bacteria in humans only resulted in modest (and not statistically significant) decreases in urine oxalate. This was partly due to horizontal gene transfer which replaced the engineered oxalate degradation pathway and partly due to the general fitness burden of the engineered oxalate degradation pathway. As such, this paper revealed a lot of important obstacles which will need to be worked on for bacterial therapies to move forward in the future.

(https://www.science.org/doi/10.1126/science.adu8000)

Precision microbiome programming for therapeutic applications is limited by challenges in achieving reproducible colonic colonization. Previously, we created an exclusive niche that we used to engraft engineered bacteria into diverse microbiota in mice by using a porphyran prebiotic. Building on this approach, we have now engineered conditional attenuation into a porphyran-utilizing strain of Phocaeicola vulgatus by replacing native essential gene regulation with a porphyran-inducible promoter to allow reversible engraftment. Engineering a five-gene oxalate degradation pathway into the reversibly engrafting strain resulted in a therapeutic candidate that reduced hyperoxaluria, a cause of kidney stones, in preclinical models.

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